Mechanism of action of hydralazine on vascular smooth muscle.

Myofibrils prepared from bovine carotid arteries were used to investigate the hypotensive action of hydralazine. These myofibrils contained an ATPase and Protein Kinase which was half-maximally activated by 1 microM Ca2+. Hydralazine inhibited Ca2+ dependent ATPase and phosphorylation. Half maximal inhibition occurred at 2 X 10(-5) M hydralazine. This inhibition was accounted for by a specific reduction in the phosphorylation of a protein which migrated with the myosin P-light chains (Mr, 20,000). Phosphorylation of the latter protein is generally thought to be obligatory for muscle contraction. Thus an inhibition of this phosphorylation by hydralazine in vivo is likely to contribute to the hypotensive action of the drug.